Tunicamycin Potentiates Antifungal Drug Tolerance via Aneuploidy in Candida albicans
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Candida albicans is a prevalent human fungal commensal and also a pathogen that causes life-threatening systemic infections. Treatment failures are frequent because few therapeutic antifungal drug classes are available and because drug resistance and tolerance limit drug efficacy.
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Caspofungin heteroresistance in C. glabrata is in sharp contrast to the mechanism described for C. albicans and C. neoformans heteroresistance, where aneuploidy is a common driver.
“This finding positions caspofungin heteroresistance in C. glabrata in sharp contrast to the mechanism described for C. albicans and C. neoformans heteroresistance, where aneuploidy is a common driver [36, 37].”
From Calcineurin‐Dependent Stress Adaptation Enables Caspofungin Heteroresistance Leading to Stable Resistance in <i>Candida Glabrata</i> (2026) · cites this paper as [36]
The Introduction (page not specified) says aneuploidy enables adaptation to caspofungin in C. albicans and to fluconazole and flucytosine in C. neoformans. It supports aneuploidy as an antifungal-adaptation mechanism in both species, but does not identify heteroresistance as the mechanism in either or establish a contrast with C. glabrata caspofungin heteroresistance. (LLM, conf=0.83)
Experimental — accuracy not yet measuredIn C. albicans, TUN induces amplification of chromosome 2, resulting in upregulation of genes associated with caspofungin tolerance, potentiating cross-tolerance to TUN and caspofungin.
“In the diploid fungal pathogen Candida albicans, TUN induces amplification of chromosome 2, which results in the upregulation of several genes associated with tolerance to caspofungin, the first-line antifungal drug. This genetic adaptation potentiates cross-tolerance to both TUN and caspofungin (Yang et al., 2021).”
From Uncovering the connection between tunicamycin-induced respiratory deficiency and reduced fluconazole tolerance in Candida glabrata (2025) · cites this paper as Yang et al., 2021
The Introduction reports that tunicamycin exposure yielded chromosome 2 duplications and that trisomy enabled tolerance to both tunicamycin and caspofungin. However, it identifies only one chromosome 2 gene, MKK2, as associated with tolerance to both drugs; the cited passages do not establish upregulation of several caspofungin-tolerance genes as the mechanism. (LLM, conf=0.86)
Experimental — accuracy not yet measuredAzole tolerance in Candida is typically temperature-independent and frequently associated with aneuploidy, which may be lost upon temperature changes or ploidy recovery.
“This tolerance is typically temperature-independent and frequently associated with aneuploidy, which may be lost upon temperature changes or ploidy recovery [114,115].”
From Insight into the Mechanisms and Clinical Relevance of Antifungal Heteroresistance (2025) · cites this paper as [115]
The Introduction associates aneuploidy with antifungal tolerance and fluconazole adaptation in C. albicans, and the Discussion describes aneuploidy as a reversible stress response (page unavailable in our copy). Neither passage establishes that azole tolerance is typically temperature-independent or that it is lost after temperature changes or ploidy recovery. The Results also caution that the aneuploid strains studied were more susceptible to fluconazole, so the paper does not establish a general association between aneuploidy and azole tolerance. (LLM, conf=0.84)
Experimental — accuracy not yet measuredExposure to hydroxyurea or tunicamycin selects for trisomy of chromosome 2 in C. albicans, which also enables tolerance to caspofungin.
“Recent work in C. albicans demonstrated that exposure to the cancer chemotherapeutic hydroxyurea, or the ER stress-inducing agent tunicamycin selects for trisomy of chromosome 2, which also enables tolerance to the echinocandin caspofungin66,67.”
From Molecular mechanisms governing antifungal drug resistance (2023) · cites this paper as [67]
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- Authors
- Yang, F., Gritsenko, V., Slor Futterman, Y., Gao, L., Zhen, C., Lu, H., Jiang, Y.-Y., & Berman, J.
- Affiliations
- Tongji University (CN)
- Tel Aviv University (IL)
- Shmunis School of Biomedical and Cancer Research, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel
- Department of Pharmacy, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China
- Corresponding author
- Berman, Judith
- Venue
- mBio
- Publisher
- American Society for Microbiology
- Published
- 2021-08-31
- Volume
- 12
- Issue
- 4
- Pages
- e0227221-e0227221
- ISSN
- 2150-7511 (ISSN-L)
- PMC
- PMC8406271
- OpenAlex
- W3196781484
- Cited by
- 59
- References
- 74
- Citations by year
- 2026: 13 · 2025: 16 · 2024: 12 · 2023: 9 · 2022: 7 · 2021: 2
- FWCI
- 2.38
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- mBio (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
- Keywords
- tunicamycin, Candida albicans, antifungal drug tolerance, aneuploidy, antifungal resistance, drug tolerance, fungal pathogens
- MeSH terms
- Aneuploidy, Antifungal Agents, Candida albicans, Stress, Physiological, Tunicamycin, Drug Resistance, Fungal
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